Non-invasive evaluation of activity in inflammatory bowel disease by power Doppler sonography

BACKGROUND: To study the vascularization in the diseased bowel wall by power Doppler sonography in patients with inflammatory bowel disease. PATIENTS AND METHODS: The diseased bowel wall was investigated in 99 patients with inflammatory bowel disease (60 patients with Crohn's disease and 39 patients with ulcerative colitis) either with active disease or in remission by B-mode and power Doppler sonography. Disease activity was determined by clinical indices. Twenty healthy age and sex matched individuals served as controls. RESULTS: Bowel wall was thickened in active Crohn's disease (mean 7 mm, range 4-14) and ulcerative colitis (mean 5 mm, range 2-15) as compared to healthy controls (mean 2 mm, range 1-3), p < 0.001. In contrast to healthy controls blood vessels were detected in the bowel wall in 100 % of patients with active Crohn's disease and 91 % with active ulcerative colitis. Vascularization was significant decreased in patients with quiescent versus active disease in ulcerative colitis (p < 0.05), while in Crohn's disease there was no significance between active and remission phase. CONCLUSIONS: Thickened and hypervascularized bowel wall are characteristic findings in inflammatory bowel disease. A combination of B-mode and power Doppler sonography offers an additional noninvasive procedure for the determination of activity in patients with inflammatory bowel disease.     

Plasma polyunsaturated fatty acid pattern in active inflammatory bowel disease.

Plasma fatty acid patterns were assessed by gas liquid chromatography in 73 patients with active inflammatory bowel disease and 107 healthy controls. The influence of the disease activity on fatty acid profile was also investigated. Plasma fatty acid patterns in patients with ulcerative colitis and Crohn's disease were similar. Plasma C18:3n3 and C22:6n3 were significantly higher in active ulcerative colitis (p = 0.0143 and p < 0.00001 respectively) and in Crohn's disease (p < 0.00001 for both) than in controls, whereas C20:3n6 was significantly lower in patients than in controls, both in ulcerative colitis (p = 0.0001) and in Crohn's disease (p = 0.0041). In more severe disease, plasma polyunsaturated fatty acid concentrations fell with a significant stepwise decrease in the desaturation index (p = 0.0031 in ulcerative colitis and p = 0.0355 in Crohn's disease). Even in patients with severe disease, however, plasma n3 fatty acids (C18:3n3 and C22:6n3) never fell below those of healthy controls. These findings suggest that in active inflammatory bowel disease, an increased biosynthesis might coexist with an increased consumption of polyunsaturated fatty acids. These observations may be of relevance in the pathogenesis of the disease as polyunsaturated fatty acids are involved in tissue eicosanoid synthesis and cellular membrane function, including that of immunocompetent cells. These results also question the rationale of using n3 polyunsaturated fatty acids in the treatment of inflammatory bowel disease.     

Increased production of vascular endothelial growth factor by intestinal mucosa of patients with inflammatory bowel disease.

BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF) is a heparin-binding glycoprotein with potent angiogenic, mitogenic and vascular permeability-enhancing activities specific for endothelial cells. Recent studies have shown significantly increased VEGF serum levels in patients with active Crohn's disease and ulcerative colitis. The origin of the circulating VEGF is not yet completely described. The present investigation examines the VEGF production of colonic mucosa in consideration of mucosal disease activity in patients with inflammatory bowel disease. METHODOLOGY: Fifteen patients with inflammatory bowel disease were studied, 9 patients with Crohn's disease and 6 patients with ulcerative colitis. Biopsies were taken from endoscopically inflamed and non-inflamed colonic mucosa. Therefore, an analysis of the spontaneous VEGF production of cultured biopsies without stimulus and of the histological grade of inflammation scored on a scale of 0-3 (normal mucosa--severe chronic colitis) were performed. Eight patients with irritable bowel syndrome served as controls. VEGF levels in the supernatant of cultured mucosal biopsies were measured using an enzyme linked immunosorbent assay. RESULTS: VEGF production is expressed as pg/mg wet weight of the biopsies. Inflamed mucosa of patients with active ulcerative colitis (16.27 +/- 10.39, p = 0.003, n = 6) and active Crohn's disease (9.88 +/- 5.98, p < 0.012, n = 9) showed a significantly higher spontaneous production of VEGF by colonic mucosa than normal mucosa of controls (3.16 +/- 1.63, n = 8). In addition, there was an increased unstimulated VEGF production by cultured inflamed mucosa of patients with Crohn's disease compared with non-inflamed mucosa (3.88 +/- 3.66, p < 0.015, n = 9). In both Crohn's disease and ulcerative colitis, there was no significant difference between VEGF production by non-inflamed mucosa and normal mucosa of controls. CONCLUSIONS: The present study identifies the intestinal mucosa as one of the origins of the elevated VEGF serum levels in patients with active inflammatory bowel disease and verifies the findings of recent studies about the importance of VEGF in Crohn's disease and ulcerative colitis.     

Microalbuminuria in inflammatory bowel disease.

Microalbuminuria independently predicts the development of nephropathy and increased cardiovascular morbidity and mortality in diabetic patients, but it may be an indicator of the acute phase response. This study examined microalbuminuria as a marker of the acute phase response in patients with inflammatory bowel disease and correlated it with the disease activity in 95 patients with inflammatory bowel disease (ulcerative colitis (n = 52), Crohn's disease (n = 43)) determined by the simple index of Harvey and Bradshaw. Fifty patients were in complete clinical remission and 45 patients had active disease. Microalbuminuria was detected in all patients with inflammatory bowel disease (147 (17) v 18 (2) microgram/min, inflammatory bowel disease v controls mean (SEM), p < 0.007). Patients with active inflammatory bowel disease had higher concentrations of microalbuminuria compared with patients in remission (206 (19) v 65 (8) microgram/min, mean (SEM), p < 0.0001). Eight patients with active inflammatory bowel disease who were sequentially followed up with measurements of microalbuminuria had significantly lower values, when the disease was inactive (active inflammatory bowel disease 192 (44) v inactive inflammatory bowel disease 64 (14) microgram/min, p < 0.03). There was a significant correlation with the simple index of Harvey and Bradshaw (r = 0.818, p < 0.0001). Microalbuminuria values were significantly lower in inflammatory bowel disease patients in remission, maintained with olsalazine compared with those patients maintained with mesalazine and salazopyrine, but no significant difference was seen in values of microalbuminuria in active inflammatory bowel disease patients receiving different salicylates. This study also measured serum amyloid-A as an indicator of the acute phase response in the same patients. Serum amyloid-A was significantly increased in active disease compared with inactive disease (151 (43) v 33 (7) or controls 11 (2) micrograms/ml, p < 0.05). In conclusion microalbuminuria is present in abnormal amounts in all patients with active inflammatory bowel disease, and values fall when the disease is quiescent. Microalbuminuria is probably a consequence of an acute phase response and provides a simple, rapid, and inexpensive test, which has the potential to monitor inflammatory bowel disease activity and response to treatment.     

Adhesion molecules in inflammatory bowel disease.

The ability of leucocytes to adhere to endothelium is essential for leucocyte migration into inflammatory sites. Some of these adhesion molecules are released from the cell surface and can be detected in serum. The soluble adhesion molecules intercellular adhesion molecule 1 (ICAM-1), E selectin, and vascular cell adhesion molecule 1 (VCAM-1) were studied in the serum of patients with Crohn's disease, ulcerative colitis, and healthy controls. A second blood sample was taken from patients with active disease after one month of treatment and a third two months after remission was achieved. Tissue expression of the same adhesion molecules was studied by immunohistology. Circulating VCAM-1 concentrations were significantly higher in patients with active ulcerative colitis (n = 11, median = 165 U/ml) compared with patients with inactive ulcerative colitis (n = 10, median = 117 U/ml, p < 0.005), active Crohn's disease (n = 12, median = 124 U/ml, p < 0.02), and controls (n = 90, median = 50 U/ml, p < 0.0001). Within each disease group there were no significant differences in E selectin or ICAM-1 concentrations between the active and inactive states, however, patients with active Crohn's disease had significantly higher ICAM-1 concentrations (n = 12, median = 273 ng/ml) than controls (n = 28, median = 168, p < 0.003). VCAM-1 concentrations fell significantly from pretreatment values to remission in active ulcerative colitis (p < 0.01). In Crohn's disease there was a significant fall in ICAM-1 both during treatment (p < 0.01) and two months after remission (p < 0.02). Vascular expression of ICAM-1 occurred more often and was more intense in inflamed tissue sections from patients with ulcerative colitis and Crohn's disease than from controls. Vascular labelling with antibody to E selectin also occurred more often in patients with active inflammatory bowel disease. In conclusion, increased circulating concentrations of selected adhesion molecules are associated with inflammatory bowel disease. There is also evidence of local upregulation, particularly of ICAM-1. Differential expression of adhesion molecules in tissue may play a part in the initiation of leucocyte migration and local inflammation; the function of circulating adhesion molecules is unknown, but may play a physiological part in blocking adhesion.     

(2'-5') oligo adenylate synthetase activity in leucocytes of patients with inflammatory bowel disease.

The activity of an interferon induced enzyme, (2',5') oligo adenylate synthetase, was determined in peripheral blood mononuclear cells and granulocytes of patients with inflammatory bowel disease and compared with its activity in cells isolated from normal subjects. In spite of the fact that circulating interferon is detected in patients with inflammatory bowel disease, we failed to see any increase in (2',5') oligo adenylate synthetase activity in these patients. The mean +/- SE enzyme activity given in nmol ATP incorporated into (2',5') isoadenylate oligomers by extracts of 10(5) peripheral blood mononuclear cells/21 hours was in normal subjects 1.84 +/- 0.30 (n = 27), in patients with active Crohn's disease 1.38 +/- 0.15 (n = 20) and in patients with active ulcerative colitis 1.14 +/- 0.23 (n = 21). (2',5') oligo adenylate synthetase activity in granulocytes was also similar in normal subjects and in patients with active ulcerative colitis or Crohn's disease. The enzyme activity in patients with active disease was similar both prior to and during steroid therapy. The low (2',5') oligo adenylate synthetase activity in peripheral blood mononuclear cells and granulocytes of patients with active inflammatory bowel disease may reflect decreased cellular response to interferon or a difference in the type of interferon elevated in viral diseases and in inflammatory bowel disease.     

Raised serum activity of phospholipase A2 immunochemically related to group II enzyme in inflammatory bowel disease: its correlation with disease activity of Crohn''s disease and ulcerative colitis.

Calcium dependent phospholipase A2 activity in the mixed micelles of 1-palmitoyl-2-oleoyl-phosphatidylglycerol and cholate was measured in sera of 39 patients with Crohn's disease, 40 patients with ulcerative colitis, and 40 healthy controls. The phospholipase A2 activity was significantly raised in those sera of the patients with active Crohn's disease and those with moderate and severe ulcerative colitis. The major phospholipase A2 activity derived from the sera was separated into two peaks by reverse phase high performance liquid chromatography. The phospholipase A2 active fractions were immunochemically characterised using specific antibody directed against human group II phospholipase A2 purified from rheumatoid synovial fluid. The results suggest that raised serum phospholipase A2 activity in patients with Crohn's disease and ulcerative colitis was mainly attributed to the two forms of phospholipase A2 immunochemically related to group II enzyme. In patients with Crohn's disease, serum phospholipase A2 activity decreased in parallel with clinical improvement, and correlated with serum C-reactive protein and erythrocyte sedimentation rate. The results suggest that serum phospholipase A2 activity may serve as an additional indicator of disease activity. Serum phospholipase A2 activity in patients with ulcerative colitis tends to increase in relation with endoscopic severity, and may be a more sensitive laboratory index than serum C-reactive protein and erythrocyte sedimentation rate to evaluate disease activity.     

Increased group II phospholipase A2 in colonic mucosa of patients with Crohn's disease and ulcerative colitis.

The immunochemical protein content of group II phospholipase A2 (PLA2) and PLA2 enzymatic activity were measured for colonic mucosal biopsy samples obtained from patients with either Crohn's disease of the colon or ulcerative colitis, and control patients without inflammatory bowel disease. Immunoreactive group II PLA2 (IR-PLA2 II) content and PLA2 activity in actively inflamed colonic mucosa of Crohn's disease patients were significantly higher than those in inactively inflamed mucosa of Crohn's disease patients and the colonic mucosa of controls. IR-PLA2 II content and PLA2 activity in severely inflamed mucosa of ulcerative colitis patients were significantly higher than those in the colonic mucosa of the controls. Mucosal PLA2 enzymatic activity was closely correlated with mucosal IR-PLA2 II content in patients with Crohn's disease and ulcerative colitis. These results suggest that an increase in PLA2 enzymatic activity in inflamed colonic mucosa of Crohn's disease and ulcerative colitis was mainly attributed to increased protein content of group II PLA2, and that an increase in mucosal group II PLA2 may be involved in the pathogenesis of intestinal inflammation of Crohn's disease and ulcerative colitis.     

Gene expression of group II phospholipase A2 in intestine in ulcerative colitis.

BACKGROUND: It has been suggested that phospholipase A2 (PLA2) has an essential role in the pathogenesis of inflammatory bowel diseases. AIMS: This study aimed at identifying cells in intestinal and mesenteric tissue samples that might express group II phospholipase A2 (PLA2-II) at the mRNA and enzyme protein levels in patients with ulcerative colitis. PATIENTS AND TISSUE SAMPLES: Tissue samples were obtained from the intestine, mesentery, skeletal muscle, and subcutaneous fat of six patients who underwent panproctocolectomy for severe ulcerative colitis. Mucosal biopsy specimens were obtained from the colon of another group of six patients with ulcerative colitis during routine diagnostic colonoscopies. Tissues from six patients without intestinal inflammatory diseases served as controls. METHODS: Tissue samples were studied by light microscopy, immunohistochemistry for PLA2-II enzyme protein, and in situ hybridisation and northern hybridisation for PLA2-II mRNA. RESULTS: PLA2-II mRNA and PLA2-II protein were detected in metaplastic Paneth cells in six patients and in the columnar epithelial cells of colonic mucosa in four out of six patients with active ulcerative colitis. Positive findings were less numerous in patients with mild ulcerative colitis. Only two out of six control patients had a weak positive signal for PLA2-II mRNA and one of these two patients had a weak positive immunoreaction for PLA2-II in columnar epithelial cells in the colonic mucosa. None of the control patients had metaplastic Paneth cells. CONCLUSIONS: Metaplastic Paneth cells and colonic epithelial cells synthesise PLA2-II in ulcerative colitis. The activity of the PLA2-II synthesis seems to be related to the degree of inflammation in the diseased bowel.     

Circulating human leucocyte elastase in patients with inflammatory bowel disease.

The plasma concentration of human leucocyte elastase (HLE), measured by enzyme immunoassay as the complex with alpha 1-proteinase inhibitor, was determined in 94 patients with active and inactive inflammatory bowel disease. In Crohn's disease and in ulcerative colitis human leucocyte elastase levels were raised significantly above normal when the disease was active, and fell on remission. The mean human leucocyte elastase level in 31 cases of active Crohn's disease was significantly greater than the mean human leucocyte elastase level in 23 patients with active ulcerative colitis (p = 0.013). The values of human leucocyte elastase correlated significantly with Crohn's disease activity index scores (p = 0.05) and with the circulating concentration of C-reactive protein (p less than 0.05 and p less than 0.01 for ulcerative colitis and Crohn's disease respectively), but not with the erythrocyte sedimentation rate. These results indicate that the concentration of human leucocyte elastase in the plasma of patients with inflammatory bowel disease reflects the activity of their intestinal disease and suggest that serial measurements of human leucocyte elastase may be useful in the assessment and clinical management of these conditions.     

Coagulation factor XIII and markers of thrombin generation and fibrinolysis in patients with inflammatory bowel disease

OBJECTIVE : To relate factor XIII levels and other prothrombotic markers to inflammatory bowel disease and investigate the frequency of valine34leucine and its effect on factor XIII cross-linking activity in patients with inflammatory bowel disease. DESIGN : Fifty patients with active inflammatory bowel disease but no venous thromboembolism (32 with ulcerative colitis, 18 with Crohn's disease), 50 patients with inactive inflammatory bowel disease but no venous thromboembolism (32 with ulcerative colitis, 18 with Crohn's disease), two age- and gender-matched healthy control groups of 100 subjects each were recruited. To further explore the relationship between valine34leucine and inflammatory bowel disease, 21 patients with the disease (13 with ulcerative colitis and eight with Crohn's disease) and venous thromoembolism (male to female ratio = 7 : 14, median age 59.5 years (range, 19-80 years)) were recruited. Two hundred and fifteen control subjects (M : F = 121 : 94, median age 62 years (28-74 years)), with venous thromboembolism (119 with deep venous thrombosis, and 96 with pulmonary embolism) were drawn from the same geographical area as the patients. METHODS : Factor XIII A, B-subunit antigen and A2B2 tetramer levels were measured using an in-house sandwich enzyme-linked immunoassay method. RESULTS : Factor XIII A2B2 tetramer and the A-subunit were significantly decreased in patients with active inflammatory bowel disease compared with controls (59% vs 95%, P < 0.0001 and 75% vs 102%, P < 0.0001, respectively), but not between the inactive inflammatory bowel disease group and controls. The D-dimer and prothrombin 1+2 fragment levels in patients with active inflammatory bowel disease were raised compared with controls (178 (152) vs 109 (84), P = 0.0007 and 82 (43) vs 55 (28), P = 0.0001, respectively). The factor XIII B-subunit and factor XIII cross-linking activity were not significantly different between patients with active or inactive inflammatory bowel disease and controls. There was no significant difference in genotype distribution in inflammatory bowel disease patients with or without venous thromboembolism and respective control subjects. Levels of tissue plasminogen activator antigen were significantly increased in patients with active inflammatory bowel disease when compared to inactive inflammatory bowel disease and controls (8.9 (3.7) vs 6.7 (3.4) vs 6.9 (3.4), P < 0.001). CONCLUSIONS : Active inflammatory bowel disease is associated with activation of coagulation. Factor XIII A and A2B2 tetramer levels were markedly decreased in active inflammatory bowel disease. Variations in the level of factor XIII in patients with inflammatory bowel disease could be multifactorial and in part may result from the increased formation of microthrombi and accelerated turnover of the factor XIII. We found no evidence of association of factor XIII valine34leucine polymorphism and inflammatory bowel disease.     

Increased absorption of polyethylene glycol 600 deposited in the colon in active ulcerative colitis.

A defect in the barrier function of the intestinal mucosa has been proposed as important in both the pathogenesis and systemic manifestations of inflammatory bowel disease. After colonoscopy, polymers of polyethylene glycol (PEG) with molecular weights of 414-810 (mean 600), were instilled in the descending colon of patients with ulcerative colitis (n = 17) and in controls without intestinal inflammation (n = 8). The patients with active ulcerative colitis (n = 6) had a significantly increased uptake of PEGs in the molecular weight range 458-810, measured as urinary excretion over the first 6 hours after instillation. The median values for their excretion were 2.85-3.80% of PEGs instilled compared with 0.32-0.94% for patients in remission (n = 11) (p < 0.05-0.01) and 0.17-0.60% for the controls (p < 0.05-0.01). The differences in absorption of PEG 414 did not reach the present level of statistical significance. There was a positive correlation between PEG absorption and the endoscopic and histological grading of inflammatory activity in the sigmoid colon (p < 0.01-0.001). These findings support a correlation between the presence of active inflammation and PEG absorption. There was little evidence to support the presence of a primary defect in the colonic barrier in patients with ulcerative colitis.     

Abnormal plasma polyunsaturated fatty acid pattern in non-active inflammatory bowel disease.

An abnormal plasma polyunsaturated fatty acid pattern (PUFA) (increased n3 and decreased n6 PUFA) has been reported in active inflammatory bowel disease (IBD). The possibility of a primary defect in the PUFA metabolism in IBD was hypothesised. The aim of this study was to assess plasma PUFA pattern in inactive inflammatory bowel disease and to ascertain whether patients who had had a colectomy and who were suffering from ulcerative colitis have a similar PUFA pattern than those patients with non-active ulcerative colitis and who had not had a colectomy. Plasma fatty acids were analysed by semi-capillary column gas-liquid chromatography in three groups of patients with inactive IBD (24 patients with inactive ulcerative colitis who had not had a colectomy, 15 patients with ulcerative colitis who had had a colectomy, and 27 patients with Crohn's disease). Plasma concentration and percentage of C22:6n3 and unsaturation index were significantly higher in patients with inactive ulcerative colitis without a colectomy and the Crohn's disease group (p < 0.0001) than in controls. Plasma concentration and percentage of C22:6n3 and the unsaturation index remained significantly higher, in both the operated and non-operated ulcerative colitis patients when compared with controls (p < 0.0001). These results suggest that in inactive IBD, an increased PUFA biosynthesis might be the cause of the high values of n3 compounds. These findings although seen in active disease, are more noticeable in remission because of the lack of artefactual factors (malnutrition, steroids, inflammation). In addition, persistence of high values in both groups of ulcerative colitis patients--that is, those who had had a colectomy and those who had not suggests the existence of a primary abnormality in the PUFA metabolism in IBD.     

血常规检查对炎症性肠病活动性判断价值

目的 探讨血常规检查能否作为国人活动性炎症性肠病的评价方法.方法 112例炎症性肠病患者和58例健康人纳入研究.所有患者均进行血常规、C反应蛋白和血沉检测.克罗恩病和溃疡性结肠炎分别依据克罗恩病疾病活动指数和Truelove-witts标准进行疾病活动状态的评价.结果 活动期克罗恩病的血红蛋白、红细胞压积、平均血小板体积明显低于缓解期患者和健康对照,差异有统计学意义（P〈0.05）,而红细胞体积分布宽度、白细胞、中性粒细胞、血小板计数则高于缓解期和健康对照,差异有统计学意义（P〈0.05）.活动期溃疡性结肠炎的血红蛋白、红细胞压积、平均血小板体积亦显著低于缓解期和健康对照,差异有统计学意义（P〈0.05）,而血小板计数高于缓解期患者,差异有统计学意义（P〈0.05）,红细胞体积分布宽度、白细胞计数高于健康对照,差异有统计学意义（P〈0.05）.白细胞、血小板计数与血沉、C反应蛋白呈正相关性（P〈0.05）,而平均血小板体积与血沉、C反应蛋白呈负相关性（P〈0.05）.结论 血常规的多项指标随疾病活动状态改变而变化,并与目前公认的反应炎症指标呈明显相关性,提示血常规可以作为判断炎症性肠病活动度的方法.     

Circulating von Willebrand factor in inflammatory bowel disease.

Raised circulating von Willebrand factor is a recognised marker of vascular injury. To evaluate the role of vascular injury in the pathogenesis of inflammatory bowel disease, serum von Willebrand factor in Crohn's disease, ulcerative colitis, confirmed bacterial diarrhoea, and healthy subjects was measured. von Willebrand factor values were raised in 9/14 patients (p = 0.007) with active Crohn's disease, 15/28 (p = 0.0004) with inactive Crohn's disease, 16/23 (p = 0.0003) with active ulcerative colitis, 9/27 (p = 0.04) with inactive ulcerative colitis, and 15/17 (p = 0.0001) patients with bacterial diarrhoea. Serum von Willebrand factor was unrelated to disease activity in Crohn's disease but was significantly raised in active (p = 0.02) compared with inactive ulcerative colitis. In contrast to controls, the detection of von Willebrand factor from inflammatory bowel disease sera and that from fractured endothelial cells was significantly inhibited by the reducing agent, dithiothreitol, suggesting the presence of an additional dithiothreitol sensitive form of the molecule derived from injured endothelial cells in inflammatory bowel disease. That serum von Willebrand factor is raised in quiescent as well as active Crohn's disease is compatible with the proposal that vascular injury is a fundamental abnormality in this disorder. The raised von Willebrand factor values in active inflammatory bowel disease and bacterial diarrhoea could be caused by either vascular injury, occurring secondary to bowel inflammation, or to an acute phase response resulting from endothelial cell stimulation by mediators released during the inflammatory process. Raised circulating von Willebrand factor could contribute to the increased risk of thrombosis associated with active inflammatory bowel disease.     

Cytokine production in patients with inflammatory bowel disease.

The production of cytokines in peripheral blood mononuclear leukocytes of patients with inflammatory bowel disease was investigated. T cell subset analysis and differential white blood cell counts were also performed. Thirty five patients with ulcerative colitis, 14 with Crohn's disease, and 15 age matched healthy volunteers were studied. No differences were observed in T cell subsets and OKT4/OKT8 ratios in patients with ulcerative colitis or Crohn's disease compared with controls. Interleukin 1 beta production was significantly increased in active ulcerative colitis and Crohn's disease, compared with values in controls, but returned to control levels in the inactive stages. In addition, in active ulcerative colitis and Crohn's disease, there were significant correlations between the interleukin 1 beta production and the ulcerative colitis activity index or Crohn's disease activity index. Interleukin 2 production was also significantly increased in the active ulcerative colitis and significantly correlated to the activity index, but there was no change in Crohn's disease patients compared with controls. Gamma interferon production in patients was the same as that in controls. This study suggests that the interleukin 1 beta and 2 values in peripheral mononuclear leukocytes of active untreated inflammatory bowel disease are indicators of the disease states of ulcerative colitis or Crohn's disease, or both.     

Increased faecal mucin sulphatase activity in ulcerative colitis: a potential target for treatment.

Colonic mucin is heavily sulphated and it has been shown that enzymatic desulphation by faecal bacterial sulphatases greatly increases its susceptibility to degradation by faecal glycosidases. A possible role for faecal mucin sulphatase in the pathogenesis of inflammatory bowel disease has therefore been explored. Faecal mucin sulphatase activity assayed using 35S mucin as substrate was increased in ulcerative colitis (median 80.2 units/g pellet weight (range 6.9-1063; 95% confidence intervals (CI): 45.2 to 293.8, n = 22) compared with 11.3 units/g (range 3.0-53.5; 95% CI: 8.7 to 29.8, n = 17) in healthy controls (p < 0.01), where one unit released 1000 dpm free sulphate/hour from 35S mucin (1680 dpm/microgram). Patients with active ulcerative colitis had higher sulphatase activity (median 146; 95% CI: 98 to 253 units/g, n = 10) than those with inactive ulcerative colitis (median 42.2; CI: 22.5 to 81.6 units/g, n = 12) (p < 0.05). Longitudinal studies in patients with ulcerative colitis show fluctuations of faecal mucin sulphatase activity corresponding to clinical disease activity in six of seven patients. Faecal mucin sulphatase activity was not significantly increased in Crohn's disease (median 36.6, range 5.7-106.6; 95% CI: 22.9 to 65.3 units/g, n = 14). The bismuth salts, bismuth subcitrate and bismuth subsalicylate were found to inhibit faecal mucin sulphatase activity at concentrations achievable therapeutically. The increased faecal mucin sulphatase activity in ulcerative colitis could be the result of greater intraluminal substrate (mucin) availability leading to bacterial enzyme induction, but would probably result in more rapid degradation of secreted mucin and represents a potential target for treatment.     

Mean platelet volume: a useful marker of inflammatory bowel disease activity

OBJECTIVES: We investigated whether the mean platelet volume would be a useful marker in the evaluation of inflammatory bowel disease activity. METHODS: Complete blood count, C-reactive protein, erythrocyte sedimentation rate, serum thrombopoietin and erythropoietin, plasma beta-thromboglobulin, and platelet factor 4 were measured in 93 patients with ulcerative colitis, 66 patients with Crohn's disease, and 38 healthy blood donors. Disease activity was assessed by the Clinical Colitis Activity Index in patients with ulcerative colitis and by the Crohn's Disease Activity Index in patients with Crohn's disease. RESULTS: Mean platelet count was increased in patients with active compared to inactive ulcerative colitis (p < 0.05), and in patients with active compared to inactive Crohn's disease (p = 0.0002) or healthy controls (p < 0.0001). On the other hand, mean platelet volume was significantly decreased in patients with active compared to inactive ulcerative colitis (p = 0.02) or healthy controls (p < 0.0001), and in patients with active compared to inactive Crohn's disease (p = 0.0005) or healthy controls (p < 0.0001). Mean platelet volume was inversely correlated with the white blood cell count (r = -0.17, p = 0.02), C-reactive protein (r = -0.46, p = 0.009) and erythrocyte sedimentation rate (r = -0.28, p = 0.008). No significant correlations were found between mean platelet volume and serum thrombopoietin or erythropoietin levels; however, a strong negative correlation between mean platelet volume and beta-thromboglobulin (r = -0.34, p < 0.0001) and platelet factor 4 (r = -0.30, p = 0.0002) was observed. CONCLUSIONS: Mean platelet volume is significantly reduced in active inflammatory bowel disease and is negatively correlated with the known inflammatory bowel disease activity markers and the platelet activation products. We propose that mean platelet volume provides a useful marker of activity in inflammatory bowel disease.     

Antineutrophil cytoplasm autoantibodies against bactericidal/permeability-increasing protein in inflammatory bowel disease.

BACKGROUND: Bactericidal/permeability-increasing protein (BPI), a constituent of primary neutrophil granules, is a potent natural antibiotic and an antineutrophil cytoplasm antibody (ANCA) antigen in cases of vasculitis in which the target antigen is neither myeloperoxidase (MPO) nor proteinase-3 (PR3). AIM: To investigate BPI as a possible target antigen for ANCAs in inflammatory bowel disease. METHODS: ANCAs were detected by routine immunofluorescence (IIF) and solid phase enzyme linked immunosorbent assay (ELISA) performed for antibodies to the purified neutrophil granule proteins; MPO, PR3, cathepsin-G, lactoferrin, and BPI in serum samples from 88 patients with inflammatory bowel disease (36 with Crohn's disease, 52 with ulcerative colitis). Thirty patients with bacterial enteritis acted as controls. RESULTS: Significantly more patients with ulcerative colitis were ANCA positive by IIF (60%) than patients with Crohn's disease (28%) or infectious enteritis (23%) (p < 0.001). IgG anti-BPI antibodies were present in 29% of patients with ulcerative colitis, 14% of patients with Crohn's disease, and 23% of patients with infectious enteritis, occurring in 44% of those patients with inflammatory bowel disease who were ANCA positive by IIF. Antibodies to other ANCA antigens were rare. The presence of ANCAs was not related to either disease activity or extent; presence of anti-BPI antibodies was significantly related to both a lower serum albumin concentration (p = 0.001) and a higher erythrocyte sedimentation rate (p = 0.02) in patients with ulcerative colitis, and to colonic involvement in patients with Crohn's disease (p = 0.01). CONCLUSION: BPI is a significant minority target antigen for ANCAs in inflammatory bowel disease that seems related to colonic Crohn's disease and disease activity in ulcerative colitis. Anti-BPI antibodies occur in infectious enteritis.